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[重组人白细胞介素-12联合粒细胞集落刺激因子对小鼠γ射线所致急性放射病的治疗作用]

[Therapeutic effect of rmIL-12 combined with G-CSF on acute radiation sickness produced by γ-ray irradiation in mice].

作者信息

Wang Li, Zhai Rui-Ren, Pang Zhao-Xia, Zhang Chao, Yu Chang-Lin

机构信息

Department of Hematology, Academy of Military Medical Sciences, Beijing, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2012 Aug;20(4):995-9.

Abstract

The aim of this study is to observe the therapeutic effect of recombinant murine interleukin 12 (rmIL-12) combining with granulocyte colony stimulating factor (G-CSF) on mice irradiated by γ-rays. 56 BALB/c mice were totally irradiated by 6.0 Gy of (60)Co γ-ray and randomly divided into irradiation control group, rmIL-12 treatment group, G-CSF treatment group and combination therapy (rmIL-12 plus G-CSF) group. rmIL-12 20 µg/kg was administrated intraperitoneally at 1 h following irradiation, and was administrated every 3 days after irradiation for 4 times in rmIL-12 treatment group. G-CSF 100 µg/kg was administrated subcutaneously the 2 h following irradiation for 14 d in G-CSF treatment group. The dose and method of rmIL-12 and G-CSF in combination therapy group were same as in rmIL-12 group and G-CSF group. The general status of mice were observed twice a day, the changes in body weight, peripheral blood cell (WBC and Plt) counts were examined once every three days, bone marrow cells were collected to perform colony cultivation on day 14 and 28 after irradiation. The results showed that WBC count recovery time in combination therapy group was significantly earlier than that of the control group (7 d vs 11 d), WBC count recovery velocity in the combination therapy group was no significant different from that of the G-CSF treatment group. Combined therapy significantly promoted Plt count recovery, resulting in less profound nadirs (16.5% vs 8.1%, P < 0.01) and rapid recovery to normal levels (11 d vs 14 d), Plt count recovery velocity in the combination therapy group was no significant different from that of the rmIL-12 treatment group. Culture of bone marrow cells in semi-solid medium also demonstrated that combination of rmIL-12 and G-CSF could stimulate bone marrow cells to form more CFU-GM and CFU-Mix than those of the irradiation control group in vitro on day 14 and 28 after irradiation (P < 0.05). It is concluded that the combination of rmIL-12 and G-CSF can significantly accelerate the recovery of hematopoietic function in mice with acute radiation sickness.

摘要

本研究旨在观察重组鼠白细胞介素12(rmIL-12)联合粒细胞集落刺激因子(G-CSF)对γ射线照射小鼠的治疗效果。将56只BALB/c小鼠用6.0 Gy的(60)Coγ射线进行全身照射,并随机分为照射对照组、rmIL-12治疗组、G-CSF治疗组和联合治疗(rmIL-12加G-CSF)组。rmIL-12治疗组在照射后1小时腹腔注射20μg/kg,照射后每3天给药1次,共给药4次。G-CSF治疗组在照射后2小时皮下注射100μg/kg,连续给药14天。联合治疗组中rmIL-12和G-CSF的剂量和方法与rmIL-12组和G-CSF组相同。每天观察小鼠的一般状况,每3天检测体重、外周血细胞(白细胞和血小板)计数的变化,在照射后第14天和28天采集骨髓细胞进行集落培养。结果显示,联合治疗组白细胞计数恢复时间明显早于对照组(7天对11天),联合治疗组白细胞计数恢复速度与G-CSF治疗组无显著差异。联合治疗显著促进血小板计数恢复,使最低点降低幅度更小(16.5%对8.1%,P<0.01),并快速恢复至正常水平(11天对14天),联合治疗组血小板计数恢复速度与rmIL-12治疗组无显著差异。半固体培养基中骨髓细胞培养也表明,照射后第14天和28天,rmIL-12和G-CSF联合应用比照射对照组在体外能刺激骨髓细胞形成更多的粒-巨噬细胞集落(CFU-GM)和混合集落(CFU-Mix)(P<0.05)。结论是,rmIL-12与G-CSF联合应用可显著加速急性放射病小鼠造血功能的恢复。

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